Table 3.
Replication Results for MWAS Top Findings, Network Findings, Candidate Gene, and Control Sitesa
| Chr | Geneb | Featurec | MWAS | Replication | |||||
|---|---|---|---|---|---|---|---|---|---|
| P Value | q Value | Samples,d No |
Position, bp | P Value | Cohende | Mean (SD) Methylation Level, % |
|||
| Top 5 MWAS findings | |||||||||
| 15 | FAM63Bf | Exon, 3′ UTR | 6.28 × 10−11 | 2.08 × 10−4 | 1075 | 59 146 738 | 3.76 × 10−12 | −0.447 | 35.55 (8.73) |
| 1065 | 59 146 744 | 7.72 × 10−12 | −0.447 | 37.11 (9.01) | |||||
| 1033 | 59 146 756 | 2.31 ×10−10 | −0.424 | 34.72 (8.49) | |||||
| 5 | ARHGAP26 | 8.19 × 10−11 | 2.08 × 10−4 | 333 | 142 138 110 | 2.96 × 10−3 | −0.274 | 28.99 (8.17) | |
| 331 | 142 138 121 | 1.03 × 10−2 | −0.216 | 25.83 (7.40) | |||||
| 315 | 142 138 140 | 5.54 × 10−3 | −0.284 | 26.76 (7.24) | |||||
| 13 | CTAGE11P | 2.05 ×10−10 | 2.27 × 10−4 | 344 | 75 795 508 | 2.71 × 10−3 | −0.285 | 40.07 (8.28) | |
| 330 | 75 795 510 | 8.04 × 10−3 | −0.355 | 44.58 (8.52) | |||||
| 22 | TBC1D22A | Intron | 2.08 ×10−10 | 2.27 × 10−4 | 335 | 47 170 345 | 6.30 × 10−3 | −0.328 | 15.25 (6.80) |
| 328 | 47 170 354 | 2.03 × 10−2 | −0.301 | 12.41 (6.46) | |||||
| 323 | 47 170 371 | 3.24 × 10−2 | −0.255 | 10.78 (5.48) | |||||
| 16 | Intergenic | 2.23 ×10−10 | 2.27 × 10−4 | 351 | 54 209 779 | 8.07 × 10−2 | −0.187 | 51.49 (8.79) | |
| 353 | 54 209 801 | 4.85 × 10−2 | −0.197 | 37.08 (8.86) | |||||
| Network findings | |||||||||
| 22 | PKDREJ/PPARAf | Exon | 1.46 × 10−9 | 7.42 × 10−4 | 1094 | 46 655 187 | 5.94 × 10−10 | −0.390 | 31.11 (8.65) |
| 14 | RCOR1 | Intron | 3.83 × 10−9 | 1.13 × 10−3 | 1082 | 103 130 134 | 1.26 × 10−10 | −0.383 | 44.55 (9.39) |
| 1069 | 103 130 138 | 2.35 × 10−8 | −0.340 | 52.26 (8.51) | |||||
| 1027 | 10 313 0147 | 5.34 × 10−1 | −0.042 | 86.87 (4.25) | |||||
| 3 | SATB1 | Intron | 8.61 × 10−9 | 1.98 × 10−3 | 330 | 18 443 092 | 3.08 × 10−2 | −0.270 | 25.64 (7.40) |
| 329 | 18 443 106 | 5.64 × 10−2 | −0.210 | 26.16 (7.11) | |||||
| 327 | 18 443 135 | 3.71 × 10−2 | −0.269 | 25.00 (6.71) | |||||
| 21 | ETS2 | Intron | 2.28 × 10−8 | 2.92 × 10−3 | 349 | 40 183 132 | 3.98 × 10−3 | −0.304 | 28.38 (7.10) |
| 19 | FCAR | Promoter | 2.36 × 10−8 | 2.92 × 10−3 | 1093 | 55 384 107 | 6.61 × 10−3 | −0.181 | 77.05 (4.77) |
| 1058 | 55 384 104 | 2.75 × 10−2 | −0.147 | 84.71 (4.30) | |||||
| 3 | FNDC3B | Intron | 4.60 × 10−8 | 3.89 × 10−3 | 189 | 171 788 002 | 9.58 × 10−4 | −0.478 | 35.51 (9.75) |
| 188 | 171 788 032 | 3.65 × 10−3 | −0.398 | 32.98 (8.27) | |||||
| 2 | CREB1/METTL21Af | Exon/intron | 1.28 × 10−7 | 6.87 × 10−3 | 1100 | 208 461 648 | 2.33 × 10−10 | −0.395 | 38.88 (9.24) |
| 1086 | 208 461 657 | 1.03 × 10−10 | −0.412 | 39.48 (9.44) | |||||
| 15 | SMAD3f | Intron | 2.09 × 10−7 | 8.69 × 10−3 | 1109 | 67 396 559 | 1.81 ×10−14 | −0.503 | 17.47 (6.45) |
| 1099 | 673 965 64 | 6.82 × 10−14 | −0.508 | 21.53 (7.34) | |||||
| 1 | ARNTf | Intron | 2.30 × 10−7 | 9.17 × 10−3 | 1087 | 150 825 039 | 1.43 × 10−9 | −0.364 | 30.38 (8.69) |
| 1011 | 150 825 079 | 7.87 × 10−4 | −0.166 | 46.70 (5.87) | |||||
| Candidate gene | |||||||||
| 7 | RELNf | Intron | 5.18 × 10−6 | 4.36 × 10−2 | 1017 | 103 576 641 | 3.14 × 10−3 | 0.107 | 92.99 (3.29) |
| 944 | 103 576 649 | 6.28 × 10−4 | 0.187 | 71.12 (6.25) | |||||
| Control sites | |||||||||
| 6 | PARK2 | Intron | 1.28 × 10−1 | 8.47 × 10−1 | 333 | 162 054 935 | 5.24 × 10−1 | 0.022 | 90.57 (2.10) |
| 330 | 162 054 989 | 3.18 × 10−1 | −0.065 | 69.26 (8.55) | |||||
| 4 | HTRA3 | Intron | 1.90 × 10−12 | 4.70 × 10−6 | 344 | 8281 202 | 9.07 × 10−1 | 0.010 | 33.93 (13.38) |
| 339 | 8281 204 | 8.40 × 10−1 | 0.042 | 33.53 (11.93) | |||||
| 6 | GMPR/ATXN1 | 4.40 × 10−12 | 4.70 × 10−6 | 1120 | 16 295 927 | 9.61 × 10−1 | −0.017 | 94.45 (4.40) | |
| 1089 | 16 295 949 | 3.81 × 10−1 | 0.005 | 95.65 (4.55) | |||||
Abbreviations: Chr, chromosome; MWAS, methylome-wide association study.
All sites selected based on MWAS top findings and network findings, as well as the RELN candidate gene, showed the same direction of effect in the MWAS and the replication. All control sites showed a positive direction of effect in the MWAS.
Gene name(s) for loci located in or within 20 kilobase (kb) from the gene.
Indicates if the loci overlap with introns, exons, untranslated region (UTR), or promoters (8 kb upstream of transcription start). None of the included sites overlapped with CpG islands (CGI) or were located within 2 kb (CGI shore) of a CGI.
Number of investigated samples in replication analysis after stringent quality control.
The mean difference between the cases and controls divided by a pooled estimate of the standard deviation, which indicates the effect size and the direction of effect. A negative d value indicates a decreased methylation level in the schizophrenia cases.
The highest (least significant) P value in the replication was significant after correction for multiple testing.